Impact of substrate elasticity on human hematopoietic stem and progenitor cell adhesion and motility

Impact of substrate elasticity on human hematopoietic stem and progenitor cell adhesion and motility
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DOI:
10.1242/jcs.095596
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发表时间:
2012-08-15
影响因子:
4
通讯作者:
Spatz, Joachim P.
Spatz, Joachim P.
中科院分区:
生物学2区
文献类型:
--
作者:
Lee-Thedieck, Cornelia;Rauch, Nicole;Spatz, Joachim P.

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在骨髓中,造血干细胞(HSC)驻留在骨内膜和血管龛中。与生态位的相互作用对于HSC数量和性质的维持至关重要。虽然这些相互作用的分子性质是很好的理解,很少有人知道的物理参数,如矩阵弹性的作用。成骨细胞,骨内膜HSC龛的主要细胞成分,在HSC动员过程中变平。我们发现,这一过程是伴随着成骨细胞硬化,表明不仅生化信号,而且机械性能的利基调制。HSC对更硬的基底的反应具有增加的细胞粘附和迁移,这可以促进HSC从龛中退出。这些结果表明,基质弹性是一个重要的因素,在调节保留的HSC在骨内膜龛,并应考虑在体外增殖HSC的临床应用的尝试。
In the bone marrow, hematopoietic stem cells (HSCs) reside in endosteal and vascular niches. The interactions with the niches are essential for the maintenance of HSC number and properties. Although the molecular nature of these interactions is well understood, little is known about the role of physical parameters such as matrix elasticity. Osteoblasts, the major cellular component of the endosteal HSC niche, flatten during HSC mobilization. We show that this process is accompanied by osteoblast stiffening, demonstrating that not only biochemical signals but also mechanical properties of the niche are modulated. HSCs react to stiffer substrates with increased cell adhesion and migration, which could facilitate the exit of HSCs from the niche. These results indicate that matrix elasticity is an important factor in regulating the retention of HSCs in the endosteal niche and should be considered in attempts to propagate HSCs in vitro for clinical applications.